Zusammenfassung
Krebs ist eine genetische Erkrankung, die mit der Aktivierung von Onkogenen und Inaktivierung von Tumorsuppressorgenen einhergeht. Neben zahlreichen genetischen und epigenetischen Alterationen proteinkodierender Gene finden sich bei Krebs außerdem Veränderungen im Expressionsmuster kleiner, nichtkodierender Ribonukleinsäuremoleküle (Mikro-RNA, miRNA). Diese 17 bis 25 Nukleotide langen miRNAs regulieren wichtige tumorzellbiologische Prozesse, wie z. B. Zellproliferation, -differenzierung, Apoptose und Metastasierung. miRNAs binden sequenzspezifisch an das nichtkodierende 3’-Ende (3’-UTR) der mRNA und unterdrücken damit die Translation oder leiten eine mRNA-Degradation ein. Es wurden bereits über 506 verschiedene miRNAs identifiziert (http://www.mirbase.org). Das menschliche Genom kodiert vermutlich >1000 miRNAs. Die Translation von ~30% aller menschlichen Gene wird von miRNAs reguliert. Jede miRNA ist im Durchschnitt gegen 200 Genprodukte gerichtet und zahlreiche miRNAs können an das 3’-UTR einer einzigen mRNA binden. Krebszellen weisen ein gegenüber nichtneoplastischen Epithelzellen verändertes miRNA-Expressionsmuster auf, das teilweise auf Veränderungen in der miRNA-Synthese zurück zu führen ist.
Abstract
Malignant tumors are characterized by multiple genetic and epigenetic alterations, which include activation and overexpression of oncogenes and inactivation of tumor suppressor genes. Recently it has become apparent that apart from genetic and epigenetic changes in classical oncogenes and tumor suppressor genes, small 17–25 nucleotides long non-coding microRNAs (miRNAs) regulate major cellular processes involved in tumor biology, such as cell proliferation, differentiation, apoptosis and metastasis. miRNAs bind through sequence-specific base pairing to the 3’ untranslated region (3’-UTR) of the mRNA leading to its translational repression or degradation, thereby negatively regulating protein expression. At least 506 different miRNAs have been identified (http://www.mirbase.org) and it is believed that the human genome encodes >1,000 miRNAs. The translation of ~30% of all human genes is regulated by miRNAs. Each miRNA targets on average 200 gene products and multiple miRNAs can bind to the 3’-UTR of a single mRNA. Evidence is increasing that the deregulation of miRNAs in malignant tumors is linked to altered expression and activity of the miRNA-biogenesis machinery.
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Röcken, C. Die Rolle der Mikro-RNA bei der Entstehung onkologischer Erkrankungen. Onkologe 17, 487–494 (2011). https://doi.org/10.1007/s00761-011-2026-8
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DOI: https://doi.org/10.1007/s00761-011-2026-8